Pacing pulse compensation

ABSTRACT

A pacemaker which generates a triphasic stimulus; the first and third phases are positive pulses, and the second is the negative stimulus. After-potentials are so low that reliable sensing of evoked signals are possible. The rapidity of the charge balancing is not affected by the stimulus amplitude because the relative amplitudes of the three phases are maintained independent of the stimulus amplitude.

This invention relates to pacemakers, and more particularly topacemakers which allow sensing of evoked potentials very soon after thegeneration of a pacing stimulus even when the same electrode is used forpacing and sensing.

The generation of any heart pacing stimulus gives rise to the storage ofcharges in body tissues. Until those charges dissipate appreciably, itis usually impossible to sense electrical activity. This is especiallytrue if the same electrode is used for both pacing and sensing. Thebeating of the heart gives rise to potentials which can be sensed.However, until the charges resulting from a pacing stimulus dissipatesufficiently, reliable sensing is impossible because the potentialsarising from those charges are so much greater than those resulting froma heartbeat.

It is standard practice in the pacemaker art to blank for manymilliseconds the sense amplifier connected to a lead over which a pacingstimulus is generated. This means that the sense amplifier cannotdetermine that the heart actually beat as a result of the stimulus.Similarly, in the case of a dual-chamber pacemaker, a ventricularblanking period is generally associated with the ventricular senseamplifier starting with the generation of an atrial stimulus; in thisway, an atrial stimulus is not mistaken as a ventricular beat. Onceagain, until the charges associated with the atrial stimulus dissipate,ventricular sensing is not possible. It has long been a goal to shortenthe blanking periods by speeding up the charge dissipation process, thussolving the "cross-talk" problem which is inherent in a dual-chamberpacemaker without impairing the sensing capability.

Toward this end, it is now common to provide what is known as activerecharge. A typical pacemaker includes a coupling capacitor in theoutput circuit. Because the net current flow through a capacitor must bezero, the provision of AC coupling insures that there is no net chargedelivered to the body tissues. The output capacitor is generally part ofthe pulsing circuitry. Charge is stored on the capacitor, and it is thendelivered rapidly over the lead when a stimulus is required. The chargedelivered then flows in the opposite direction through the capacitoruntil the charges in body tissues are dissipated. In order to speed upthe charge neutralization, an "active" recharge circuit can be used toconnect the output capacitor through a transistor switch to a potentialsource. This causes a larger reverse current to flow through thecapacitor, and the charges stored in the body tissues dissipate morerapidly. Negative pulses are most often used to stimulate the heart.Thus with an active recharge circuit, the pacing cycle consists of anegative pulse followed by a positive pulse.

A recent development is that of providing a precharge positive pulse inaddition to a postcharge positive pulse. This technique is described inU.S. Pat. Nos. 4,343,312 and 4,373,531. The total charge deliveredduring the two positive pulses equals the charge delivered during thenegative pulse in the opposite direction; in this way the net charge iszero. Although it is not described in these two patents why theprovision of a positive precharge pulse together with a positivepostcharge pulse is better than the latter alone, even when the combined"area" under both pulses in the first case is equal to the "area" underthe single pulse in the latter case, there is no question that thestored charges dissipate more rapidly. My analysis shows that the reasonfor this has to do with the space charges delivered by the electrode.The process can be thought of as three spherical wavefronts emanatingfrom a point source. The magnitudes of the wavefronts and theirseparations can be adjusted so that soon after the launching of the lastwavefront, the net potential at the point source approaches zero.Unfortunately, the circuits disclosed as exemplary in the twoabove-identified patents can only be implemented in practice withdifficulty.

It is an object of our invention to provide a pacing system which, withminimum controls, allows safe, reliable sensing of the capture of theheart (atrium or ventricle).

It is another object of our invention to provide a pacing system whichallows the complex process of polarization elimination to be realized inintegrated form.

It is another object of our invention to provide a pacing system inwhich single-ended or differential sensing of evoked potentials isaccomplished by the same elements which eliminate the electrodepolarization.

It is another object of our invention to provide a pacing system inwhich the balancing of electrode polarization is achieved with a singlesetting which is then independent of changes in pacing voltageamplitude.

It is still another object of our invention to eliminate "cross-talk" ina dual-chamber pacemaker without impairing the sensing capability.

The method of our invention, by which the after-potential at a pacingelectrode following the generation of a pacing stimulus is minimized,entails the use of a differential amplifier to sense cardiac activity.The pacemaker stimulating and reference electrodes are connected to theinputs of the amplifier. A triphasic stimulus is generated, with thefirst and third phases being of one polarity and the second being of theopposite polarity. The first and second phases are delivered through acapacitor and the voltage drives which are provided have amplitudeswhich are substantially proportional to each other. The first phasebegins with a quiescent voltage across the capacitor. The third phaseutilizes the voltage across the capacitor to drive a current through thecapacitor and the stimulating electrode until the voltage across thecapacitor equals the starting quiescent voltage.

This technique is to be distinguished from that disclosed, for example,in the above-identified patents. The prior art technique really worksonly in the case of steady-state pacing. At the start of each pacingcycle, there is some initial voltage across the output capacitor. Ifpacing pulses are continuously generated at a fixed rate, somesteady-state condition is eventually reached with the capacitor voltageat the end of the cycle being equal to the capacitor voltage at thestart of the cycle. The result is very fast charge balancing, asdesired. But if the heart is not paced steadily, the capacitor voltagedrops as the result of leakage through the capacitor and in the printedcircuit board on which it is mounted. The result is that for the firstnumber of cycles that the heart is paced, the charge balancing is notsufficient to allow the sensing of evoked potentials. In our invention,however, sensing of evoked potentials is possible the first time thatthe heart is paced, even if it has not been paced for hours before that,i.e., the advantages of the invention apply even to an isolated stimuluscycle. Capture of the heart can be sensed immediately, even followingthe generation of the first pacing pulse. Another difficulty with theprior art technique is that the charge balancing, and therefore thesensing of an evoked potential, is dependent upon the stimulusamplitude. As the amplitude is changed, for example, using aconventional external programmer, adjustments must be made to the chargebalancing circuit. In our invention, the adjustment is automatic. Moreaccurately, no adjustment need even be made.

Further objects, features and advantages of the invention will becomeapparent upon consideration of the following detailed description inconjunction with the drawing, in which:

FIG. 1 is a block diagram of an overall pacemaker in which the system ofour invention may be incorporated;

FIGS. 2A and 2B, with FIG. 2A being placed to the left of FIG. 2B,depict the illustrative embodiment of our invention--the circuitryincluded in the sensing and polarization controller block 15 of FIG. 1;

FIG. 3 is a table which characterizes he operations of the switches ofthe circuit of FIGS. 2A and 2B;

FIG. 4 depicts the form of the triphasic pacing pulse generated by thecircuit of FIGS. 2A and 2B; and

FIGS. 5-10 depict the operative components of the circuit of FIGS. 2Aand 2B which are involved during different phases of the systemoperation, and will be helpful in understanding the system operation byfocusing attention on only those elements whose understanding isnecessary in each case.

The pacemaker of FIG. 1 is depicted in a highly symbolic block-diagramform. Microprocessor 11 controls all of the other blocks. The telemetryblock 14 is conventional in today's pacemakers, and allows bothadjustment of pacemaker parameters from an external programmer, and thetransmission of information from the pacemaker which is indicative notonly of accumulated data, but even a signal representative of theinstantaneous sense signal. Present-day sophisticated telemetry circuitsallow for the interrogation of stored diagnostic data, and thederivation of real-time operational data.

The analog-to-digital block 12 is provided with a signal called ANLG₋₋CMP from the sensing and polarization controller 15. The ANLG₋₋ CMPsignal is a 2-level waveform at the Q output of flip-flop 52 in FIG. 2B.As will be described, the sequence of bits which comprise the signalrepresents increases and decreases in the sense signal. The A/D block 12acts on this signal, under control of the microprocessor, to deriveinformation about the sense signal. The ANLG₋₋ CMP waveform, of course,is derived in accordance with operations of block 15 on the two leads 16which are extended to the heart, as will be described.

The microprocessor has a direct connection to the sensing andpolarization controller block 15, and the signals over this direct linkcontrol the various switches depicted in FIGS. 2A and 2B. In addition,output generator 13 provides a potential over its output lead extendedto block 15. In connection with FIGS. 2A and 2B, the potential islabeled 0₋₋ TNK. This potential represents the magnitude of the negativephase of the stimulating pulse. As will be described, the circuitry ofFIGS. 2A and 2B which corresponds to block 15 of FIG. 1 permits rapidcharge balancing independent of the magnitude of the 0₋₋ TNK signal.

The circuit of FIGS. 2A and 2B is shown in solid lines and dashed lines.The solid lines represent those elements included in the integratedcircuit which are at the heart of block 15 of FIG. 1. The dashed linesare the external components which are too large to be fabricated on thechip. Connections to the integrated circuit are made via the pins whichare depicted in the drawing. For example, at the top of FIG. 2A acapacitor 20 is shown in dashed lines. This 0.15 uF capacitor is toolarge to be fabricated on the integrated circuit. For this reason it isin the form of an external component connected across integrated circuitpins PA₋ REF and PA₋₋ IN (which labels represent a preamplifierreference pin and a pre-amplifier input pin).

Before describing the circuit operation, it will be helpful to make afew general remarks. There are 22 switches labeled SW1 through SW22.Depending on the mode in which block 15 of FIG. 1 is being operated, asdetermined by microprocessor 11, some of the switches are open and theothers are closed. FIG. 3 depicts those switches which are open andclosed in each mode of operation. It is to be understood that all of theswitches are active circuits on the integrated circuit chip.

Referring to FIG. 2A, pin 28 is connected to the tip lead, and the PACEpin is connected through external capacitor 26 to the tip lead. The tipis the lead connected to the electrode in the heart which provides thenegative stimulus. It will be noted that there are two pins labeled CASEand RING. If a bipolar lead is used, the indifferent electrode can beeither the ring or the case. If a unipolar electrode is used, then theindifferent electrode must be the case. The pin labeled CASE isconnected electrically to the case; the pin labeled RING is connected tothe ring electrode only if a bipolar lead is employed. In the event abipolar lead is used, it is the positions of switches 1 through 4 whichdetermine which of the two possible indifferent electrodes (CASE orRING) is operative.

It should be noted that, as depicted in the table of FIG. 3, switches 5,6, 7, 19 and 20 are all open or closed together. The first threeswitches control the connection of the two possible anodes (case orring) and the stimulating lead (tip) to the reference ground. During ECGProcessing (sensing), all three of these switches are closed, as areswitches 19 and 20. The latter two switches are closed in order that adelta modulator (on FIG. 2B) function, and the former three switches areclosed to connect each of the three inputs through a 200K resistor toreference ground. At all other times, according to the table of FIG. 3,the five switches are open. Switches 19 and 20 are held open so that thedelta modulator function as a sample-and-hold circuit. Switches 5, 6 and7 are similarly held open because it is not desired that current flowthrough the case, ring or tip and the respectively connected 200Kresistors to reference ground. During the various phases involved inpacing, and even in the alert and sensor drive modes, current pulses areapplied by the pacemaker and it is undesirable for any of the current tobe allowed to flow through the 200K resistors. The provision of separateswitches for the case and ring inputs allows a dual-chamber pacemaker tobe made, using duplicates of the circuits of FIGS. 2A and 2B, but toeven have the different chambers paced in different modes--unipolar orbipolar. [Using two of the circuits in a dual-chamber pacemaker,switches 19 and 20 in one would be open even when a pacing stimulus isgenerated by the other; the object is to monitor the electrogram signalfor each chamber only when neither chamber is being paced so that it isonly cardiac activity which is analyzed.]

Capacitor 20 is a standard coupling capacitor which is used to block DCon the electrodes and to prevent the DC offset voltage of operationalamplifier 22 from being amplified. Operational amplifier 22 has a gainof 30 when switch 10 is open, this being the ratio of the feedbackresistor, between the output of the amplifier and the minus input, tothe input impedance connected to the minus input. The operationalamplifier functions to equalize the two signals at its minus and plusinputs. However, in practice it is not possible to achieve this, andthere is some offset voltage across the plus and minus inputs ofoperational amplifier 22. This offset voltage is stored on capacitors 20and 26.

Capacitor 26 is the standard-type AC coupling capacitor for generatingthe stimulus. FIG. 4 depicts the form of the triphasic pacing stimulusas it appears at the PACE pin. The positive pre-charge pulse is in theform of a ramp. While a ramp is not essential, it is preferred becauseit has been shown empirically that the operation of the circuit is lessdependent on the stimulus amplitude when a ramp precharge pulse is usedrather than a rectangular precharge pulse. Also, it is commonly acceptedthat a sharp positive pulse is more likely to trigger tachycardia if itis applied during a T wave. However, the present invention is notlimited to the use of a ramp potential for the precharge pulse.Similarly, it is known that a beat can be triggered with a positivepulse, and therefore the polarities of the three phases of the stimulusshown in FIG. 4 can be reversed. However, it is preferred that themiddle phase be negative, as shown, because it is generally acknowledgedthat less energy is required to pace the heart if a negative stimulus isused.

The amplitude of the stimulus is the magnitude of the vertical line inFIG. 4 between the horizontal base line and the lowermost extent of thenegative stimulus. This magnitude is labeled 0₋₋ TNK, and it isdetermined by the magnitude of the potential at node 24. This potentialmay vary between 0 and 7.5 volts in the illustrative embodiment of theinvention. [Node 24 is not shown as a pin. The reason for this is thatin the actual implementation of the system of FIG. 1, it is notnecessary that the separations between blocks 12, 13 and 15 be exactlyas shown. The 0₋₋ TNK potential at node 24 may be derived from stillother circuits included in the same chip which contains the circuit ofFIGS. 2A and 2B, but these elements are not important for anunderstanding of the present invention. Therefore, the operative inputis simply labeled 0₋₋ TNK at a node 24, without paying concern to theadditional elements connected between the node and input pins.Similarly, in the actual implementation of the invention, the circuitryat the far right of FIG. 2B, including comparator 50 and current sources38 and 40, may be actually included in A/D block 12 of FIG. 1. Theinvention has nothing to do with the particular circuit partitioningwhich is employed.]

The 0₋₋ TNK value can be fixed by an external programmer. Alternatively,energy can be conserved if the stimulus amplitude is caused by themicroprocessor to track the threshold. How the 0₋₋ TNK magnitude isdetermined has no bearing on use of the present invention. It isassumed, however, that the 0₋₋ TNK potential is derived from acapacitor. In such a case, the capacitor would discharge slightly duringapplication of the negative stimulus. That is why FIG. 4 shows thenegative pulse decreasing slightly in magnitude during the course of thestimulus.

The waveform of FIG. 4 is not drawn to scale. The precharge period has aduration of about 3 milliseconds, the postcharge interval has a durationof about 8 milliseconds, the width of the negative stimulus is about 0.5milliseconds, and a blanking interval of 300 microseconds (to allow thecircuit to settle after switching) follows the overall cycle. Thewaveform represents the potential at the PACE pin.

Capacitor 32, connected to the RMP₋₋ CAP pin, serves to generate theramp waveform which controls the shape of the precharge pulse shown inFIG. 4. Although it is only 3 nF in magnitude, it is still too large tobe integrated and it is therefore an external component. Capacitor 30,which serves as a charge pump, as will be described, is small enough tobe integrated.

The ALERT pin at the lower left of FIG. 2A is used to drive apiezoelectric crystal which serves as a sonic alarm. The ALERT circuithas no bearing on the present invention, and is shown only because it ispart of the integrated circuit. The patient actually hears a beep, andis warned to seek medical attention. The physician programs themicroprocessor to trigger the alarm under specified conditions. Toactually sound the alarm, the microprocessor alternately operatesswitches 21 and 22. In the illustrative embodiment of the invention, itis the 0₋₋ TNK voltage at node 24 which actually drives the crystal.Referring to FIG. 3, it will be seen that when the ALERT pin is to bedriven high, switch 21 is closed, and when it is to be driven low,switch 22 is closed so that the pin can be connected to circuit ground.Switch 1 is closed during the alert sequence; the case is grounded andthus the return path for the current is through the case. All otherswitches (except switches 11, 13, 17 and 18--to be discussed below) areopen; in the table of FIG. 3, the absence of a code letter is indicativeof the respective switch being open.

As far as the table of FIG. 3 itself is concerned, the switch conditionswhich are represented will be understood as the detailed operation ofthe system is described. However, the various modes of operation shouldbe appreciated before contemplating the detailed circuitry. The ECGProcessing mode represents conventional sensing. The Blanking moderepresents the state of the switches during the time that sensing isdisabled following a stimulus cycle.

The four phases of a pacing pulse, as depicted in FIG. 4, are separatelylisted in the table of FIG. 3 -Precharge, Stimulus, Active Postcharge,and Blanking. While it is true that the sense amplifier is blankedduring the generation of a stimulus, the table entries for the Blankingmode apply only when the other entries do not, e.g., when sensing is tobe disabled even in the absence of pacing.

The Passive Postcharge mode of operation is not ordinarily employed. Inthe event, however, that Active Postcharge is not desired, PassivePostcharge may be used, as will be described.

The Alert Drive High and Alert Drive Low modes of operation have alreadybeen described. The last two modes are similar and have to do withsensing functions. For example, periodically, e.g., ten times persecond, a sensor associated with the patient's respiration may beinterrogated. See, e.g., U.S. Pat. No. 4,702,253, entitled"Metabolic-Demand Pacemaker" issued on Oct. 27, 1987. Two differentmodes of operation are set forth in the table of FIG. 3 because thedrive for the sensor may be through the case or the ring, and one ofswitches 1 or 2 is closed for this purpose.

Returning to the general description of the circuit of FIGS. 2A and 2B,the resistor network at the left of FIG. 2B is a standard R-2R laddertype network, with standard binary weightings. The network serves as anattenuator and thus controls sensing sensitivity. An 8-bit register (notshown) is set by the microprocessor to control the sensitivity, and the8 switches in the ladder network have their positions controlled by thebits in this register. The sensitivity can be programmed by thephysician, or it can be adjusted automatically by the microprocessor. Ingeneral, if the sensitivity is too low, a heartbeat may not be sensed;if the sensitivity is too high, noise may be erroneously interpreted asa heartbeat. Automatic sensitivity adjustment has no bearing on thepresent invention, and the attenuator of FIG. 2B is shown only becauseit is included in the integrated circuit in which the subject inventionis implemented.

In FIG. 2B, there are three capacitors 54, 56 and 60, and resistor 58,all of which are external components. These elements are connectedbetween three pins, PCMP₋₋ IN (positive comparator input), NCMP₋₋ IN(negative comparator input), and FIL₋₋ IN (filter input). In ourcopending application entitled "Combined Pacemaker Delta Modulator andBandpass Filter," filed on even date herewith, these four externalcomponents are described. The four components and the attenuator outputimpedance function as a standard bandpass filter, as usually found in apacemaker sense amplifier, and also at the heart of a delta modulator.The capacitors are external because they are too large to be integrated.Resistor 58 is also an external component because this allows greatercontrol over its value.

In the illustrative embodiment of our invention, a form of deltamodulation is utilized. The Q output of flip-flop 52, extended to nodeANLG₋₋ CMP, is a two-level signal which is derived from the signal atthe tip lead after attenuation by the ladder network. The input signalis applied to the plus input of comparator 50. The output sequencefollows the input signal in the sense that the output represents a 1when the input is increasing, and it represents a 0 when the input isdecreasing. When the input is not changing, the output bits alternate invalue. The technique of delta modulation in general is described inMoney et al U.S. Pat. No. 4,466,440 which issued on Aug. 21, 1984.References may also be made to Money et al U.S. Pat. Nos. 4,448,196which issued on May 15, 1984; 4,509,529 which issued on Apr. 9, 1985;and 4,527,133 which issued on July 2, 1985.

The input signal which is operated upon by a delta modulator can bereconstructed by causing a fixed-size step to be taken for each bitsample, the direction of the step depending upon the bit-sample value.As long as the delta modulator operates at a fast enough rate, thereconstructed signal will follow the input signal. Before proceedingwith a description of the subject invention, the delta modulator shownon FIG. 2B will be described.

The heart of the delta modulator is the comparator 50, flip-flop 52, andtwo oppositely-poled current sources 38 and 40 connected between thenegative and positive voltage supplies. The outputs of the flip-flopcontrol switches 46 and 48. (Although not shown, it is possible todisable both switches by including a control gate in lines 42 and 44;these lines are symbolic only, and represent the flip-flop control overgates 46 and 48.) When switch 46 is closed, current flows up throughconstant-current source 38; when switch 48 is closed, current flows downthrough con- stant-current source 40.

The operation of a delta modulator can be best understood by firstconsidering a different circuit, one in which the input signal from theattenuator is applied through capacitor 54 to the minus input ofcomparator 50, as shown, but with the plus input of the comparator beingconnected to a reference potential and otherwise disconnected from thecircuit. Suppose, for example, that the input signal starts to decreasefrom some quiescent level. This tends to cause the potential at theminus input of the comparator to fall, and the output of the comparatorgoes high. The D input of flip-flop 52 is thus high, and the next 32Kclock pulse causes the Q output of the flip-flop to go high. Switch 48closes and current flows from source 40 to the left through capacitor54. This tends to restore the potential at the minus input of thecomparator to the reference level. In a similar manner, switch 46 closesto control a left-to-right current flow through the capacitor when theinput signal increases from a quiescent level and the output ofcomparator 50 goes low to reset flip-flop 52. The state of the flip-flopis controlled in accordance with the current bit sample. Since the twooutputs of the flip-flop control current flows from respective currentsources, the output of the comparator not only represents a bit sampleindicative of the manner in which the input signal is changing, but italso controls the current sources as required.

The minus comparator input is a virtual ground. It is maintained by theoperation of feedback at the potential of the reference potentialconnected to the positive comparator input. Capacitor 54 is charged anddischarged by the current sources so that the potential at the output ofthe attenuator has added to it or subtracted from it a capacitorpotential such that the resulting ,level at the minus input of thecomparator equals the reference potential. If a steady-state conditionhas been achieved, with alternating 0 and 1 bit samples appearing at theANLG₋₋ CMP output node, and then there is a sudden change in thepotential at the output of the attenuator, a number of bit samples ofthe same value will be generated until the capacitor has charged ordischarged to an extent which compensates for the change at the outputof the attenuator. The number of bit samples of constant value at theoutput of the delta modulator thus represents the magnitude of thechange in the input signal, with the value of the output bitsrepresenting the direction of the change.

Instead of connecting the plus input to a reference potential as justdescribed, however, we connect the plus input of the comparator to theinput. Also, we connect capacitors 56 and 60, and resistor 58, acrossthe inputs of the comparator. Most pacemakers and sense amplifiers havea bandpass filter consisting of two capacitors and two resistors. Butthe typical bandpass filter also includes an amplifier. In order toachieve a filter Q value greater than 1, either inductors must be usedor an amplifier is necessary. A delta modulator also requires anamplifier and a capacitor. As far as the circuit of FIG. 2B isconcerned, there is no savings in components since a delta modulator(requiring one capacitor) and a filter (requiring two capacitors and tworesistors) would still require the same number of components shown inthe drawing--three capacitors and two resistors. The savings is in theuse of a single amplifier, comparator 50, instead of the two which wouldotherwise be required--one for the delta modulator and the other for thefilter. The main advantage of achieving both delta modulator and filterfunctions with the use of a single active device is that less power isrequired to operate the pacemaker.

As far as the delta modulator is concerned, the details of its operationare not necessary for an understanding of the present invention. Infact, the circuit of FIG. 2B may be thought of in general terms ascomprising an attenuator followed by a delta modulator. All that has tobe known about the circuit is that switches 19 and 20 are both open atall times other than during sensing, as shown in the table of FIG. 3.This is done to prevent a change in the voltage across the capacitors,the delta modulator thus serving as a sample-and-hold circuit duringblanking and whenever else the activity which is to take place is otherthan standard sensing.

What goes on during the ECG Processing mode is depicted in FIG. 5. Theformat of FIG. 5 is followed in the other figures. Only those componentsare depicted which are important for an understanding of the operationbeing described. [The delta modulator itself is shown as having a singleswitch for connecting either of the current sources to capacitor 54 forthe sake of simplicity. Similarly, the attenuator at the left of FIG. 2Bis shown as a block 36 in FIG. 5.] With respect to the CASE and RINGpins of FIG. 2A, they are shown in FIG. 5 in a different form. One ofthem serves as the anode and the other is what can be termed an "unusedanode." The case or the ring is the anode in each case, depending uponthe positions of switches 3 and 4. Referring to FIG. 3, it will be notedthat during ECG Processing both of switches 1 and 2 are open. Similarly,both of switches 5 and 6 are closed. As seen in FIG. 2A, each of the twopossible anodes is thus connected through a 200K resistor to referenceground. Which of the two anodes is connected to the PA₋₋ REF pin dependsupon which of switches 3 and 4 is closed. As indicated in FIG. 3, in thecase of unipolar sensing, in which the case serves as the anode, switch3 is closed and switch 4 is open. On the other hand, with bipolarsensing, switch 4 is closed and switch 3 is open. In either case, theeffective anode is connected through a 200K resistor to referenceground, and to capacitor 20. This 200K resistor, and the 200K resistorconnected to tip pin 28 in FIG. 2A, keep the electrodes from driftingmore than a few millivolts from ground potential.

Operational amplifier 22 is arranged as a standard differential circuitwith an AC coupling capacitor 20, but with one important difference.Because of the 3M resistor connected between the output of the amplifierand the minus input, and the provision of a 100K resistor at the input,the gain of the amplifier is 30. The plus input of the amplifier issimilarly provided with a 100K resistor and a 3M resistor connected toground. In this standard configuration, if the same potential changeoccurs at the left end of each of the 100K resistors, there will be nochange in the output of the amplifier. What is unusual about the circuitof FIG. 5 is the 3M resistor which is connected between the PACE pin andcapacitor 20. There is some offset voltage between the plus and minusinputs of operational amplifier 22. Current flows up through capacitor26 in FIG. 5 until the capacitor charges to this offset voltage. (Thecapacitor actually charges to the offset voltage plus 1/31 times the tipvoltage due to the voltage divider relationship of the resistorsconnected to the plus input. A potential of 1/31 of the tip voltage istypically a few microvolts and can be ignored. The reason formaintaining the offset voltage across the capacitor will become apparentbelow.

Aside from this unconventional connection of capacitor 26, the circuitoperation is relatively straightforward. A differential amplifiercircuit is used to derive an electrogram signal which is thenattenuated; after attenuation, the delta modulator operates on thesignal in a manner that, insofar as the subject invention is concerned,is conventional.

It should be noted that in accordance with the table of FIG. 3, duringECG Processing switch 11 is closed; this allows the tip to be connectedto the plus input of operational amplifier 22 so that sensing can takeplace. Switch 13 is closed to connect ramp capacitor 32 to referenceground. This is shown in FIG. 5. The capacitor is held discharged inpreparation for the generation of a ramp which will in turn control theshape of the precharge pulse. Switches 17 and 18 are both closed so thatcapacitor 30 is connected between reference ground and the 0₋₋ TNKpotential. Capacitor 30 serves as a charge pump, as will be described,and initially it is held at the 0₋₋ TNK potential until it is needed.

Referring to the table of FIG. 3, the next mode of operation is that ofBlanking, and this mode is shown in FIG. 6. Because switch 19 is open,the delta modulator is in effect disconnected from the attenuator.Because switch 20 is open, the delta modulator capacitor potentials aresimply held. It should be noted that neither of current sources 38 and40 is shown as being connected to capacitor 54 during blanking. Althoughflip-flop 52 continues to be clocked, neither current source isconnected to the capacitor. (It will be recalled that in connection withcontrol lines 42 and 44 of FIG. 2B, it was mentioned that both ofswitches 46 and 48 could be held open.)

Although the drawing of FIG. 6 is designed to show what happens duringblanking, the anode connections are labelled so that the alert andsensor modes are also depicted. During blanking, all of switches 1through 6 are open and thus the two possible anodes are disconnectedfrom the circuit. Depending upon whether a unipolar or bipolar lead isused, one of the two possible anodes is disconnected altogether. Buteven the other anode is also disconnected when sensing is blanked. Theindication "or other channel" in the label for the operative anode ismeant to imply that if a dual-chamber pacemaker is constructed inaccordance with the principles of the invention, the anode associatedwith one chamber is blanked even when the other channel is paced. Theanode label in FIG. 6 also states, that the anode which is used isgrounded during alert and sensor functions. This results from one ofswitches 1 or 2 being closed, as indicated in the table of FIG. 3; areturn path for the current used for the alert or sensor function isthus provided. (During the alert mode, switch 1 is closed so that thecurrent return is through the case. The piezoelectric crystal used forthe alert tone is mounted on the inside of the case, and that is why thecase is used for the current return. In the sensor mode, however, thereturn path can be through the case or the ring. Reference may be madeto application Ser. No. 787,125 referred to above. The ring is in theheart, and use of the ring as the anode allows better measurement ofminute volume. If all that is desired is a measurement of therespiratory rate, however, it is more advantageous to use the case asthe anode.)

During blanking, ramp capacitor 32 is still connected at both ends toreference ground, and the 0₋₋ TNK potential still appears across pumpcapacitor 30. When the system is blanked, potential changes at the tipare reflected at the output of amplifier 22. However, they have noeffect on the system operation because sensing is blanked. Capacitor 26remains charged to the offset voltage of amplifier 22.

In the event a heartbeat is not detected by the end of the conventionalescape interval, a pacing stimulus is generated. The three phases of thestimulus are shown in FIG. 4. The first phase is known as precharge, andthe equivalent circuit during this phase of operation is shown in FIG.7. Referring to FIG. 2A and the table of FIG. 3, one of switches 1 or 2is closed so that the operative anode is connected to ground. Becauseswitch 10 in FIG. 2A is closed, the resistor in the feedback path ofamplifier 22 is shorted out. That is why the output of amplifier 22 inFIG. 7 is shown as being connected directly to the minus input. Withswitch 12 closed, the ramp capacitor 32 is connected between the plusinput of the amplifier and ground. Also as depicted in the table of FIG.3, switch 14 is closed so that capacitor 26 is connected to the outputof the amplifier. Insofar as understanding the configuration of FIG. 7is concerned, there remains to consider switches 15-18. As indicated inthe table of FIG. 3, switches 15 and 16 are closed when switches 17 and18 are open, and vice versa. The two pairs of switches change stateunder control of the 32K clock. Referring to FIG. 2A, it will be notedthat with switches 17 and 18 closed, the pump capacitor is connectedbetween the 0₋₋ TNK potential and ground. When switches 15 and 16 areclosed, the capacitor is connected between the plus input of theamplifier and the output.

When the pump capacitor 30 is connected between ground and the 0₋₋ TNKnode, the right side of the capacitor

negatively (0₋₋ TNK is a negative potential). When charges the variousswitches cycle so that the capacitor is connected across the operationalamplifier as shown in FIG. 7, the amplifier itself functions as a unitygain buffer since the output is connected to its minus input. Currentflows through capacitor 30 from right to left, and down through rampcapacitor 32 to charge it positively. The current discharges pumpcapacitor 30, and charges the ramp capacitor until the pump capacitor isdischarged. All of the charge on the pump capacitor is transferred tothe ramp capacitor. Assuming that the 0₋₋ TNK potential is across a 6.8uF capacitor, the full voltage is transferred to the pump capacitor. Butthe potential transferred to the ramp capacitor is inversly proportionalto the relative capacitances of the ramp and pump capacitors. With themagnitudes shown, each step in the ramp is 1/300 of the 0₋₋ TNKpotential. The step size remains substantially constant. The slope ofthe ramp depends upon both the rate at which the steps are applied,i.e., the 32K clock, and the step size.

The ramp potential which develops across capacitor 32 is buffered byamplifier 22 so that a positive potential is extended through capacitor26 to the tip electrode. The duration of the precharge pulse isdetermined by the microprocessor. For each kind of lead, the prechargeperiod can be determined by laboratory testing; the surface capacitanceof an electrode varies with the material of which it is made and howthat material has been treated. The stimulus of FIG. 4 can be appliedover any lad in question to a saline solution. By converting the ANLG₋₋CMP pulse sequence back to an analog signal, the precharge duration canbe adjusted to give a minimal potential on the lead following the8-millisecond postcharge interval to be described below. The postchargeduration is arbitrarily selected at 8 milliseconds, since this is shortenough to allow the evoked signal to be sensed. With a postchargeduration of 8 milliseconds, a typical precharge period is around 3milliseconds. (It is to be understood that the various phases of FIG. 4are not shown to scale.)

The operational amplifier during the precharge mode of operationreproduces the ramp potential which develops across capacitor 32, but itdoes so with a low output impedance so that current is driven into thetip lead. Capacitor 26 must be able to withstand a reverse voltage ofabout three volts; with a VDD supply of 2.8 volts, the maximumoperational amplifier output is less than three volts. Initially, thereis an offset potential across capacitor 26, as described in connectionwith FIG. 5. The offset potential may be of either polarity. The voltageacross the capacitor may change polarity as the capacitor charges duringthe precharge phase.

With a programmable pacemaker, one of the parameters which a physicianmay be allowed to control is the duration of the precharge (althoughthis is not shown in the drawing). With telemetry, the physician is ableto observe the electrogram signal which is sensed. The physician maygradually reduce the pacing pulse amplitude as he observes the sensedsignal until capture is lost. At that point, what he observes followingthe postcharge period is the artifact which is sensed 8 millisecondsafter the generation of a stimulus. The precharge interval may then beadjusted so that the artifact is minimized. It is also contemplated thatthe entire sequence can be automated so that the pacemaker automaticallyadjusts the duration of the precharge period. As will be described, theparticular circuitry of our invention allows for automatic chargebalancing, no matter what the pacing pulse amplitude, i.e., no matterwhat the magnitude of the 0₋₋ TNK potential. But this by itself does noteliminate the artifact following the postcharge period. What isnecessary for this is that the charges delivered during the two positivephases have a ratio such that the potential at the point source is zero.It is expected that one day mechanisms will be developed for allowingthe pacemaker to automatically adjust the relative charge levelsdelivered during the two positive phases to enhance sensing of an evokedsignal following the postcharge phase.

The circuit operation during the stimulus phase is shown in FIG. 8.Referring to the table of FIG. 3, it will be observed that switch 8 isnow closed instead of open, and switch 14 is open rather than closed.Referring to FIG. 2A, the opening of switch 14 disconnects the output ofthe operational amplifier from the tip lead, and the closing of switch 8connects the capacitor across which the 0₋₋ TNK potential is developedto output capacitor 26. The 0₋₋ TNK capacitor now discharges to generatethe negative stimulus. During the course of the pulse, the capacitordischarges slightly, as is known in the art, and it is for this reasonthat the negative stimulus in FIG. 4 is shown decreasing in amplitudeduring its approximately 0.5-millisecond duration. This tapering of theamplitude of the pulse could be minimized by using a capacitor largerthan the conventional 6.8 uF capacitor which is typically used. However,a larger capacitor would require more volume. Also, with a largercapacitor it would take longer to change the 0₋₋ TNK potential if themicroprocessor decides that the pacing pulse amplitude requires change.

It should be noted that switches 15-18 still generate a ramp voltageacross capacitor 32. It is totally unimportant, however, because theoutput of amplifier 22 is no longer connected to the PACE pin.

The active postcharge phase is shown in FIG. 9. Switch 14 is closed onceagain so that the output of amplifier 22 drives the tip lead. Theamplifier is now used to generate the third phase, a positive pulse, andthe amplifier output must be connected to the PACE pin. Switch 8 is nolonger closed, so the 0₋₋ TNK potential no longer drives the tip lead.With switch 11 closed, the plus input of the amplifier is connected tothe junction of 3M and 100K resistors, as depicted in FIG. 9. Finally,capacitors 30 and 32 are restored to the quiecsent conditions, with theramp capacitor being completely discharged and the pump capacitor havingthe 0₋₋ TNK potential placed across it in preparation for another cycle.It is the circuit of FIG. 9 which requires the closest scrutiny.

Referring to the table of FIG. 3, during the active postcharge switch 10is closed so that the output of amplifier 22 is connected to the minusinput. Switch 11 is closed so that the tip is connected through a 100Kresistor to the plus input of the amplifier. The other switches whichare closed maintain the potentials across capacitors 30 and 32 at theirquiescent levels. Capacitor 26 forces charge balancing, as comparablecapacitors have done in the prior art, by virtue of the fact that therecan be no net current which flows through the capacitor and thus the tiplead. (The capacitor is also a safety factor because it prevents DC frombeing applied to the heart, something which would otherwise be fatal inthe event of certain malfunctions of the integrated circuit.) In theprior art, in order to speed up the dissipation of charges stored inbody tissues, following the generation of a negative stimulus the rightside of capacitor 26 might be connected to ground. In fact, this isprecisely what is shown in FIG. 10 for what is termed passivepostcharge. In the event an active postcharge is not desired, as shownin the table of FIG. 3 switch 9 is closed rather than switch 14.Referring to FIG. 2A, this causes the right side of capacitor 26 in FIG.10 to be connected to ground rather than to the output of operationalamplifier 22 as in FIG. 9. During active postcharge, however, it is thevoltage across the capacitor which drives the operational amplifier tonot only discharge the capacitor, but also to dissipate chargesremaining in body tissues.

The left side of the capacitor is connected through a 100K resistor tothe plus input of the amplifier. The resistor is necessary for safetypurposes; it limits the current which can be delivered to the tipelectrode even if the plus input of the amplifier is shorted to thetypically 2.8-volt supply. (The current is further limited by the 200Kresistors which couple the anodes to ground through switches 5 and 6during normal ECG processing; switches 1 and 2 are deliberately keptopen so as not to short the case and the ring to ground.) Referring toFIG. 9, the 100K and 3M resistors form a voltage divider so that 30/31of the capacitor voltage appears across the inputs of the operationalamplifier. The output of the amplifier is driven positively and currentflows to the left through the capacitor and the tip lead. The currentwaveform is substantially independent of the body impedance throughwhich the current flows.

The output of the operational amplifier is connected to the PACE nodethrough switch 14, even though the switch is not shown in the drawing ofFIG. 9. The switch typically as an impedance of about 100 ohms. Theimpedance of the body seen by the tip electrode is similarly in theorder of a few hundred ohms. (That is why the current flow throughcapacitor 26 is into the body, and not through the 100K resistor.) Atthe start of the active postcharge, the voltage at the tip lead risesinstantaneously as shown in the waveform of FIG. 4; the actual step inthe potential depends upon the ratio of the body impedance to the switchimpedance. As shown in FIG. 4, the peak positive potential at the startof the postcharge phase is slightly higher than the peak of the ramp atthe end of the precharge phase. However, depending on the ratio of theimpedances, and the magnitude of the charge delivered during theprecharge phase, the postcharge peak could be smaller than the prechargepeak.

In any event, the current which flows during the active postchargeperiod enters the right side of the capacitor and exits the left side.Current stops flowing when an equilibrium condition is reached. At thistime, the potential across the capacitor will be equal to the offsetvoltage across the two inputs of the amplifier. This is exactly the samecondition that was described above in connection with the ECG processingdiagram of FIG. 5. It will be recalled that while the system is sensingcardiac activity, capacitor 26 is charged to the offset potential. Whatthis means is that at the end of the postcharge phase, the capacitor hasthe identical charge that it had just before the precharge phase. This,in turn, means that charge balance has been achieved. More important,the charge balance has been achieved very quickly, because during thebalancing process the potential across the capacitor causes theamplifier to actively drive the potential in the opposite direction.

It should be noted that with an impedance for switch 14 of 100 ohms, thetime constant of the charging circuit, taking into account the fact thatcapacitor 26 has a magnitude of 6.8 uF, is only 0.68 millisecond. Thismeans that well before the postcharge duration of 8 milliseconds, chargebalancing is achieved. When passive postcharge is employed, the rechargeinterval is much longer, as in the prior art. Typically, it requires50-150 milliseconds before sensing becomes reliable once again. Thisshould be compared with the 8-millisecond active postcharge period ofthe invention. The largest part of the evoked potential following thegeneration of a negative stimulus occurs during the first 30milliseconds following the stimulus. Thus, use of the invention allowsmost of the evoked potential to be sensed.

In the prior art, in the context of only a single positive pulse(following the negative stimulus) being provided, it was suggested toreturn a capacitor, such as the right side of capacitor 26, to apositive supply. The problem with this is that there is no way ofknowing how long the connection should be maintained. It is not enoughto make the positive and negative pulse phases equal in duration becausethe impedance of the body tissues is generally lower during the positivephase than during the negative phase; thus, the charges which would flowin the two directions while the capacitor is connected to two supplieswould not necessarily be equal, and it would take longer until theremaining charges dissipate. In the invention, on the other hand, anactive drive is provided to control the balancing until, and only until,the balancing is achieved; it is known when the charge has been balancedbecause the capacitor drives the postcharge phase only until it is inexactly the same condition that it was before the precharge phase. Whatis more, the postcharge phase takes place while a small time constantcharacterizes the output circuit, so that reliable sensing can resumewell before the evoked potential has disappeared.

It should now be apparent why capacitor 26 in FIG. 5 is connected in therather strange configuration referred to above. The configuration shownin FIG. 5 insures that the potential across the capacitor is equal tothe offset potential of amplifier 22. The only reason for developingthis potential across the capacitor during ECG processing is that thisis the potential which develops across the capacitor when postcharge iscompleted. This feature, however, is not critical, especially if theoffset potential of the operational amplifier is low. Perhaps the mostimportant aspect of the invention is the provision of the standardcoupling capacitor in the feedback path of the operational amplifier sothat the capacitor is rapidly driven, with all of the current flowingthrough the capacitor and the body. In this way, the driving currentstops automatically when the capacitor is returned to its quiescentcondition, and because all of the current flows through the body, thebody has also been returned to its quiescent condition.

Another important feature of the invention is that the precharge currentvaries with the magnitude of the 0₋₋ TNK potential and so does theamplitude of the stimulus. As described above in connection with theprecharge drawing of FIG. 7, the 0₋₋ TNK potential determines theamplitude of the precharge pulse. Similarly, as described in connectionwith the stimulus drawing of FIG. 8 and the waveform of FIG. 4, the 0₋₋TNK potential determines the amplitude of the negative stimulus. Thus,varying the 0₋₋ TNK potential does not affect the charge balancing atall. The charge delivered during the precharge phase is proportional tothe charge delivered during the stimulus. In general, it is sufficientif the charges are substantially proportional to each other, that is, ifthe two charges are proportional to each other to within 10%. Asdescribed above, for reliable sensing to take place very shortly afterthe negative stimulus, it is not enough that the net charge be zero.What is also important are the relative amounts of charge in the twopositive wavefronts. This is a function of the timing of the threephases in each cycle. The duration of the precharge pulse is controlledto maximize performance. The charge and timing relationships willthereafter not be affected by changing the 0₋₋ TNK potential becausethis potential determines the charges delivered during the first twophases in a proportional manner.

The invention is also applicable to biphasic pulses, in which there isan active postcharge pulse but no precharge pulse. In the prior art, thecharge delivered during the postcharge period was dependent upon theimpedance of the body. Because the body impedance varies, chargebalancing could not be controlled during the active period. The couplingcapacitor would always insure charge balancing, but a longer time wouldbe required for it because there was no way for the circuit to knowexactly when to stop the active postcharge, i.e., when charge balancingwas achieved. In the circuit of the subject invention, however, even inthe absence of a precharge pulse, active postcharge persists until, andonly until, charge balance is achieved--substantially independent of thebody impedance.

Although the invention has been described with reference to a particularembodiment, it is to be understood that this embodiment is merelyillustrative of the application of the principles of the invention.Numerous modifications may be made therein and other arrangements may bedevised without departing from the spirit and scope of the invention.

We claim:
 1. A pacemaker stimulus-generating circuit comprising anelectrode, a coupling capacitor, and means for controlling an isolatedstimulus cycle including means for causing a negative stimulatingcurrent to flow to said electrode through said capacitor, and meansdriven by the capacitor voltage for applying a subsequent positivecurrent to said electrode through said capacitor until the capacitorvoltage returns to its value prior to the start of the isolated stimuluscycle, said positive current applying means operating to apply a currentwhich is a function of said capacitor voltage but which is substantiallyindependent of the body load impedance to which said electrode iscoupled.
 2. A pacemaker stimulus-generating circuit in accordance withclaim 1 further including means for generating a positive current flowthrough said capacitor and said electrode immediately prior to the flowof said negative stimulating current.
 3. A pacemaker stimulus-generatingcircuit in accordance with claim 2 wherein during each cycle ofoperation the net charge delivered to said electrode is zero.
 4. Apacemaker stimulus-generating circuit in accordance with claim 3 furtherincluding means for varying the amplitude of said negative stimulatingcurrent, and means for controlling the positive charge delivered to saidelectrode immediately prior to the flow of said negative stimulatingcurrent to be substantially proportional to the negative chargedelivered during the flow of said negative stimulating currentindependent of said amplitude.
 5. A pacemaker stimulus-generatingcircuit in accordance with claim 4 wherein the positive current flowimmediately prior to the flow of said negative stimulating current is inthe form of a ramp waveform.
 6. A pacemaker stimulus-generating circuitin accordance with claim 5 wherein the amplitude of said ramp waveformand the amplitude of said negative stimulating current are substantiallyproportional to each other, and the duration of said ramp waveform issuch that the after-potential at said electrode is minimized immediatelyafter said subsequent positive current is applied.
 7. A pacemakerstimulus-generating circuit in accordance with claim 5 wherein theamplitude of said ramp waveform and the amplitude of said negativestimulating current are substantially proportional to each other, andthe duration of said ramp waveform is such that the after-potential atsaid electrode immediately after said subsequent positive current isapplied is low enough to allow reliable sensing at said electrode of aheartbeat signal evoked by said negative stimulating current.
 8. Apacemaker stimulus-generating circuit in accordance with claim 4 whereinthe ratio of charges delivered to said electrode prior and subsequent tosaid negative stimulating current is such that the after-potential atsaid electrode immediately after said, subsequent positive current isapplied is low enough to allow reliable sensing of a heartbeat signalevoked by said negative stimulating current.
 9. A pacemakerstimulus-generating circuit in accordance with claim 3 wherein saidpositive current applying means includes an operational amplifier withsaid capacitor connected in the feedback path thereof, said operationalamplifier causing a positive current to flow until the capacitor voltageis reduced sufficiently to support the offset potential which appearsacross the inputs of said operational amplifier.
 10. A pacemakerstimulus-generating circuit in accordance with claim 9 further includingmeans for controlling said operational amplifier to function as a senseamplifier, and means operative while said amplifier functions as a senseamplifier for simultaneously developing across said capacitor apotential which is equal to the potential which appears across saidcapacitor at the termination of said subsequent positive current flow.11. A pacemaker stimulus-generating circuit in accordance with claim 3wherein said positive current applying means includes an operationalamplifier with said capacitor connected in the feedback path thereof.12. A pacemaker stimulus-generating circuit in accordance with claim 11further including means for controlling said operational amplifier tofunction as a sense amplifier.
 13. A pacemaker stimulus-generatingcircuit in accordance with claim 12 further including means operativewhile said operational amplifier functions as a sense amplifier todevelop a potential across said capacitor which equals the potentialwhich remains across said capacitor at the termination of saidsubsequent positive current flow.
 14. A pacemaker stimulus-generatingcircuit in accordance with claim 13 wherein said negative current andsaid positive currents have amplitude and time relationships such thatthe after-potential at said electrode immediately after said subsequentpositive current is applied is low enough to allow reliable sensing atsaid electrode of a heartbeat signal evoked by said negative stimulatingcurrent.
 15. A pacemaker stimulus-generating circuit in accordance withclaim 3 wherein said negative current and said positive currents haveamplitude and time relationships such that the after-potential at saidelectrode immediately after said subsequent positive current is appliedis low enough to allow reliable sensing at said electrode of a heartbeatsignal evoked by said negative stimulating current.
 16. A pacemakerstimulus-generating circuit in accordance with claim 1 wherein saidpositive current applying means includes an operational amplifier withsaid capacitor connected in the feedback path thereof, said operationalamplifier causing a positive current to flow until the capacitor voltageis reduced sufficiently to support the offset potential which appearsacross the inputs of said operational amplifier.
 17. A pacemakerstimulus-generating circuit in accordance with claim 16 furtherincluding means for controlling said operational amplifier to functionas a sense amplifier, and means operative while said amplifier functionsas a sense amplifier for simultaneously developing across said capacitora potential which is equal to the potential which appears across saidcapacitor at the termination of said subsequent positive current flow.18. A pacemaker stimulus-generating circuit in accordance with claim 1wherein said positive current applying means includes an operationalamplifier with said capacitor connected in the feedback path thereof.19. A pacemaker stimulus-generating circuit in accordance with claim 18further including means for controlling said operational amplifier tofunction as a sense amplifier.
 20. A pacemaker stimulus-generatingcircuit in accordance with claim 19 further including means operativewhile said operational amplifier functions as a sense amplifier todevelop a potential across said capacitor which equals the potentialwhich remains across said capacitor at the termination of saidsubsequent positive current flow.
 21. A pacemaker stimulus-generatingcircuit comprising an electrode, a coupling capacitor, and means forcontrolling an isolated stimulus cycle including means for generating apositive current flow through said capacitor and said electrode, meansfor causing a negative stimulating current to flow to said electrodethrough said capacitor, and means driven by the capacitor voltage forapplying a subsequent positive current to said electrode through saidcapacitor until the capacitor voltage returns to its value prior to thegeneration of said positive current at the start of the isolatedstimulus cycle, means for varying the amplitude of said negativestimulating current, and means for controlling the amplitude of saidpositive current flow immediately prior to the flow of said negativestimulating current to be a substantially fixed proportion of theamplitude of said negative stimulating current independent of saidamplitude.
 22. A pacemaker stimulus-generating circuit in accordancewith claim 21 wherein the positive current flow immediately prior to theflow of said negative stimulating current is in the form of a rampwaveform.
 23. A pacemaker stimulus-generating circuit in accordance withclaim 22 wherein the amplitude of said ramp waveform and the amplitudeof said negative stimulating current are substantially proportional toeach other, and the duration of said ramp waveform is such that theafter-potential at said electrode is minimized immediately after saidsubsequent positive current is applied.
 24. A pacemakerstimulus-generating circuit in accordance with claim 22 wherein theamplitude of said ramp waveform and the amplitude of said negativestimulating current are substantially proportional to each other, andthe duration of said ramp waveform is such that the after-potential atsaid electrode immediately after said subsequent positive current isapplied is low enough to allow reliable sensing at said electrode of aheartbeat signal evoked by said negative stimulating current.
 25. Apacemaker stimulus-generating circuit in accordance with claim 21wherein the ratio of charges delivered to said electrode prior andsubsequent to said negative stimulating current is such that theafter-potential at said electrode immediately after said subsequentpositive current is applied is low enough to allow reliable sensing of aheartbeat signal evoked by said negative stimulating current.
 26. Apacemaker stimulus-generating circuit in accordance with claim 21wherein said positive current applying means includes an operationalamplifier with said capacitor connected in the feedback path thereof.27. A pacemaker stimulus-generating circuit in accordance with claim 26further including means for controlling said operational amplifier tofunction as a sense amplifier, and means operative while said amplifierfunctions as a sense amplifier for simultaneously developing across saidcapacitor a potential which is equal to the potential which appearsacross said capacitor at the termination of said subsequent positivecurrent flow.
 28. A pacemaker stimulus-generating circuit in accordancewith claim 21 wherein said negative current and said positive currentshave amplitude and time relationships such that the after-potential atsaid electrode immediately after said subsequent positive current isapplied is low enough to allow reliable sensing at said electrode of aheartbeat signal evoked by said negative stimulating current.